Confirmatory Testing After Positive RPR for Syphilis
After a positive Rapid Plasma Reagin (RPR) test for syphilis, a treponemal-specific test such as TP-PA (Treponema pallidum particle agglutination) or FTA-ABS (fluorescent treponemal antibody absorption) should be performed as confirmatory testing. 1
Understanding Syphilis Testing Algorithms
There are two main testing approaches for syphilis:
Traditional Algorithm:
- Initial screening with nontreponemal test (RPR or VDRL)
- Confirmation of positive results with treponemal-specific test
Reverse Sequence Algorithm:
- Initial screening with treponemal test
- Confirmation of positive results with nontreponemal test
When an RPR test is positive, confirmatory testing is essential because nontreponemal tests can yield false-positive results in various conditions.
Recommended Confirmatory Tests
The CDC recommends the following treponemal tests for confirmation after a positive RPR 1:
TP-PA (Treponema pallidum particle agglutination) - preferred option due to:
- High sensitivity (95-100%)
- Excellent specificity (100%)
- Superior sensitivity compared to FTA-ABS, especially in primary syphilis
Other acceptable options:
- FTA-ABS (fluorescent treponemal antibody absorption)
- EIA (enzyme immunoassay)
- CIA (chemiluminescence immunoassay)
Performance of Confirmatory Tests
Treponemal tests have different performance characteristics 1, 2:
| Test | Sensitivity | Specificity | Notes |
|---|---|---|---|
| TP-PA | 95-100% | 100% | Preferred for adjudicating discordant results |
| FTA-ABS | 78.2-95% | 95-100% | Less sensitive for primary syphilis |
| EIA/CIA | 95-100% | 95-100% | Excellent sensitivity across all stages |
Important Considerations
False-positive RPR results occur more commonly in:
- Women (0.27% vs 0.20% in men)
- Patients over 60 years (0.34% vs 0.25% in younger patients) 1
Discordant results (treponemal reactive/nontreponemal nonreactive) should be confirmed with additional treponemal testing to rule out false positives 1
Clinical context is crucial for interpretation, especially in:
- Previously treated syphilis (treponemal tests typically remain positive for life)
- Early primary syphilis (tests may be negative)
- Neurosyphilis evaluation (requires CSF testing)
After Confirmation
Once syphilis is confirmed, additional steps include:
- Staging based on clinical presentation and history
- Treatment with appropriate penicillin regimen based on stage
- Follow-up testing with quantitative nontreponemal tests at 3,6,9, and 12 months to monitor treatment response 1
- Partner notification and treatment
Pitfalls to Avoid
- Don't rely solely on nontreponemal tests for diagnosis as they lack specificity
- Don't use treponemal tests to monitor treatment response as they typically remain positive for life
- Don't confuse reinfection with treatment failure when titers increase after initial decline
- Don't miss neurosyphilis evaluation in patients with late latent syphilis, CD4 count <350 cells/mm³ with high-titer VDRL (>1:32), or treatment failure 1